The aim of this proposal is to elucidate the mechanisms that link changes in renal vascular resistance and glomerular filtration to tubular sodium chloride reabsorption, "tubulo-glomerular feedback". Both infusion of hypertonic saline and induction of metabolic acidosis reduce proximal tubular fluid reabsorption and cause vasoconstriction and a decrease in GFR. The auto-transplanted dog kidney will be used to determine if changes in reabsorption and filtration are linked through release of a vasoactive mediator into the periglomerular renal interstitium. Thus, it is planned to (1) measure possible mediators released into the interstitium of the renal cortex by collecting the complete output of lymph from the auto-transplanted dog kidney. In lymph, components of the renin-angiotensin and prostaglandin systems and adenosine will be measured. If the inciting stimuli cause the kidney to release a mediator into the interstitium, (2) its relationship to distal nephron reabsorption will be examined by blocking distal reabsorption with diuretics. In addition, (3) the relationship of the mediator to vasoconstriction will be examined by using specific antagonists of the mediator. The results of these studies will be used to analyze the interrelationship between the glomerular microcirculation and tubular reabsorption of sodium chloride in the rat using micropuncture methods. By measuring determinants of glomerular filtration (4) the anatomical locations of changes in vascular resistance and glomerular filtration associated with changes in tubular reabsorption will be determined. Finally, after applying the two stimuli, (5) specific antagonists of designated mediators will be used to study the importance of the mediator in changing vascular resistance and determinants of glomerular ultrafiltration.